Related Experiment Video
Updated: May 3, 2026
11:56
Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
14.3K
Near-Field Terahertz Nanoscopy Spatially Resolves Chiral Drug-Cell Interactions: Toward Precision Intracellular
Xitian Hu1, Yadi Wang2, Yue Wang3
1Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Terahertz Technology Innovation Research Institute, Shanghai Key Lab of Modern Optical System, University of Shanghai for Science and Technology, Shanghai 200093, China.
Analytical Chemistry
|June 5, 2025
Summary
Chiral drug enantiomers show different effects within cells. Terahertz scattering-type scanning near-field optical microscopy (THz s-SNOM) revealed nanoscale drug distribution and cellular changes, advancing chiral pharmacology.
Area of Science:
- Pharmacology
- Biophysics
- Cell Biology
Background:
- Chiral drug enantiomers possess distinct pharmacological profiles, yet their subcellular distribution and mechanisms remain poorly understood due to detection limitations.
- Traditional methods cannot resolve nanoscale drug distribution within cells, hindering the study of enantiomer-specific effects and cellular responses.
- Understanding subcellular drug distribution is crucial for developing safer and more effective chiral therapeutics.
Purpose of the Study:
- To investigate single-cell response heterogeneity to chiral drug exposure using nanoscale imaging.
- To analyze morphological and biochemical differences induced by RS-ibuprofen and its individual enantiomers at the subcellular level.
- To establish a novel nanoscale paradigm for mapping drug-cell interactions and understanding chiral pharmacology.
Main Methods:
- Utilized terahertz scattering-type scanning near-field optical microscopy (THz s-SNOM) for label-free, nanoscale imaging of cellular responses.
- Systematically analyzed morphological and biochemical compositional changes in cells treated with RS-ibuprofen, (R)-(-)-ibuprofen, and (S)-(+)-ibuprofen.
- Employed principal component analysis and Euclidean distance distribution for spectral variation analysis in intracellular and nuclear regions.
Main Results:
- Drug-treated cells showed increased plasma membrane-derived extracellular vesicles (PEVs) area (24.6%–39.9%).
- Distinct spectral variations were identified in intracellular and nuclear regions, with enantiomers inducing different heterogeneity patterns.
- RS-ibuprofen treatment led to increased membrane heterogeneity and decreased nuclear heterogeneity, with significant quantitative spectral intensity differences in nuclear regions (p < 0.001).
Conclusions:
- THz s-SNOM enables nanoscale mapping of drug-cell interactions, revealing enantiomer-specific subcellular responses.
- Chiral drug enantiomers induce fundamentally different heterogeneous evolution patterns within cellular compartments.
- This approach advances subcellular chiral pharmacology by conceptualizing drug-cell interactions as spatially encoded phenomena.
